1. ATP-gated P2X3 receptors constitute a positive autocrine signal for insulin release in the human pancreatic β cell.
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Jacques-Silva, M. Caroline, Correa-Medina, Mayrin, Cabrera, Over, Rodriguez-Diaz, Rayner, Makeeva, Natalia, Fachado, Alberto, Diez, Juan, Berman, Dora M., Kenyon, Norma S., Ricordi, Camillo, Pileggi, Antonello, Molano, R. Damaris, Berggren, Per-Olof, and Caicedo, Alejandro
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ADENOSINE triphosphate , *INSULIN , *PANCREATIC beta cells , *GLUCOSE , *IN situ hybridization , *IMMUNOHISTOCHEMISTRY techniques , *WESTERN immunoblotting , *AUTOCRINE mechanisms - Abstract
Extracellular ATP has been proposed as a paracrine signal in rodent islets, but it is unclear what role ATP plays in human islets. We now show the presence of an ATP signaling pathway that enhances the human β cell's sensitivity and responsiveness to glucose fluctuations. By using in situ hybridization, RT-PCR, immunohistochemistry, and Western blotting as well as recordings of cytoplasmic-free Ca2+ concentration, [Ca2+]i, and hormone release in vitro, we show that human β cells express ionotropic AlP receptors of the P2X3 type and that activation of these receptors by ATP coreleased with insulin amplifies glucose-induced insulin secretion. Released ATP activates P2X3 receptors in the β-cell plasma membrane, resulting in increased [Ca22+] and enhanced insulin secretion. Therefore, in human islets, released ATP forms a positive autocrine feedback loop that sensitizes the β cell's secretory machinery. This may explain how the human pancreatic β cell can respond so effectively to relatively modest changes in glucose concentration under physiological conditions in vivo. [ABSTRACT FROM AUTHOR]
- Published
- 2010
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